Project Summary There is wide-spread recognition that `binge' alcohol consumption is associated with increased cardiovascular risk, but much of this is based on epidemiological studies and mechanisms remain poorly understood. Sympathetic overactivity has been suggested as a potential mechanism for alcohol-mediated cardiovascular disease, but direct evidence is lacking. The proposed project represents our first step in the pursuit of a long- term goal to explore alcohol-mediated hypertension, stroke, and sudden cardiac death, and practical interventions that might reduce the incidence of these cardiovascular conditions. The proposed project focuses on the impact of evening alcohol consumption on nocturnal and early morning autonomic function and reactivity in male and female binge drinkers. In aim 1, will determine the effect of evening alcohol consumption on nocturnal autonomic control and sympathetic neural responsiveness the subsequent morning. Aim 2 will determine the influence of sex (male vs. female) and the ovarian cycle (early follicular vs. midluteal phase) on sympathetic neural responsiveness to evening alcohol in humans. Aim 3 will determine if continuous positive airway pressure (CPAP) blunts alcohol-mediated sympathoexcitation at night and early morning. An exploratory aim will determine if autonomic responses to alcohol and CPAP are associated with affective states and psychomotor performance. Our central hypothesis is that evening alcohol consumption will elicit sympathetic overactivity at night and the subsequent morning, and that this sympathoexcitation will be augmented women and blunted after CPAP treatment. The novelty and innovation of this project is that our mechanistic aims are bolstered with an interventional aim that includes a randomized, control trial (CPAP vs. sham-CPAP). The project utilizes established, gold-standard methods for assessing sleep (polysomnography) and sympathetic neural activity and reactivity (microneurography). In summary, this project will determine the impact of simulated `binge' alcohol consumption on neural cardiovascular function at times of elevated cardiovascular risk (i.e., sleep and early morning) in male and female binge drinkers, and test a potential therapeutic strategy (i.e., CPAP) to blunt alcohol-induced autonomic dysfunction.